Aerobic Exercise Activates AMPK/PGC-1α Pathway, Inhibits Cardiomyocyte Apoptosis Improves Mitochondrial and Infarcted Heart Function

Dokl Biochem Biophys. 2024 Oct;518(1):420-428. doi: 10.1134/S1607672924600556. Epub 2024 Aug 28.

Abstract

Aerobic exercise (AE) has attracted considerable research attention as a non-invasive therapeutic tool in recent years. Accumulating evidence has revealed its protective role against a wide range of diseases. In this study, we aimed to establish whether AE could inhibit apoptosis in infarcted cardiomyocytes and protect the heart. AE in post-myocardial infarction (post-MI) mice improved their cardiac and physical functions. Transmission electron microscopy of myocardial tissue and adenosine 5'-triphosphate (ATP) assay findings revealed an increased mitochondrial number but decreased ATP content in the post-MI mice. Notably, this change was significantly reversed by AE. Immunofluorescence/ TUNEL staining assay results showed that AE inhibited cardiomyocyte apoptosis. Using immunoblotting of myocardial tissues, we found that AE increased the level of the anti-apoptotic protein Bcl-2/Bax, significantly decreased the expression of the pro-apoptotic protein caspase-3, and activated the AMPK/PGC-1α signaling pathway. Our findings provide evidence that AE activates the AMPK/PGC-1α signaling pathway, improves mitochondrial energy supply capacity, and effectively inhibits apoptosis in cardiomyocytes. Therefore, AE can be considered a promising post-infarction therapeutic intervention.

Keywords: AMPK; Aerobic exercise; Apoptosis; Cardiac rehabilitation; Myocardial infarction; PGC-1α.

MeSH terms

  • AMP-Activated Protein Kinases* / metabolism
  • Animals
  • Apoptosis*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • Mitochondria, Heart / metabolism
  • Myocardial Infarction* / metabolism
  • Myocardial Infarction* / pathology
  • Myocytes, Cardiac* / metabolism
  • Myocytes, Cardiac* / pathology
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha* / metabolism
  • Physical Conditioning, Animal*
  • Signal Transduction*

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • AMP-Activated Protein Kinases
  • Ppargc1a protein, mouse